The four and a half LIM domain protein 3, also named the LIM-protein FHL3, belongs to the LIM-only family. Based on the special structure of LIM-only proteins, FHL3 can perform significant functions in muscle proliferation and cardiovascular diseases by regulating cell growth and signal transduction. In recent years, there has been increasing evidence of a relation between FHLs and tumor biology, since FHL3 is often overexpressed or downregulated in different cancers. On the one hand, FHL3 can function as a tumor suppressor and influence the expression of downstream genes. On the other hand, FHL3 can also play a role as an oncoprotein in some cancers to promote tumor progression via phosphorylation. Thus, FHL3 is proposed to have a dual effect on cancer progression, reflecting its complex roles in cancer. This review focuses on the roles of FHL3 in cancer progression and discusses the interaction of FHL3 with other proteins and transcription factors. Finally, the clinical significance of FHL3 for the treatment of cancers is discussed.

BackgroundCurrently, the main treatment for lower extremity artery disease (LEAD) is revascularization, including endovascular revascularization (EVR) and open surgical revascularization (OSR), but the specific revascularization strategy for LEAD is controversial. This review provided the comprehensive and recent evidence for the treatment of LEAD.MethodsMedline, Embase, and the Cochrane Library databases were searched for relevant articles. Randomized controlled trials (RCTs) and cohort studies comparing the short-term or long-term outcomes between EVR and OSR of LEAD were identified. Short-term outcomes were 30-day mortality, major amputation, wound complication, major adverse cardiovascular events (MACEs), and length of hospital stay (LOS), while long-term outcomes included overall survival (OS), amputation-free survival (AFS), freedom from re-intervention (FFR), primary patency (PP), and secondary patency (SP).Results11 RCTs and 105 cohorts involving 750,134 patients were included in this analysis. For the pooled results of cohort studies, EVR markedly decreased the risk of 30-day mortality, wound complication, MACEs, LOS, but increased the risk of OS, FFR, PP, and SP. For the pooled outcomes of RCTs, EVR was associated with obviously lower 30-day mortality, less wound complication and shorter LOS, but higher risk of PP, and SP. However, both RCTs and cohorts did not show obvious difference in 30-day major amputation and AFS.ConclusionsBoth the pooled results of cohorts and RCTs indicated that EVR was associated with a lower short-term risk for LEAD, while OSR was accompanied by a substantially lower long-term risk. Therefore, the life expectancy of LEAD should be strictly considered when choosing the revascularization modality. As the current findings mainly based on data of retrospective cohort studies, additional high-quality studies are essential to substantiate these results.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022317239.

Objective The influence of diabetes mellitus (DM) on mortality following lower extremity amputation (LEA) remains controversial. This systematic review and meta-analysis aimed to determine the influence of DM on longterm mortality (LTM) and short-term mortality (STM) after amputation. Materials and methods The Medline, the Cochrane library, and Embase databases were searched. The primary and secondary outcomes were LTM and STM following amputation. One-year and 30-day all-cause mortality after amputation were considered as LTM and STM, respectively. A random-effects model was utilized to pool results. To evaluate the stability of results, subgroup analyses and sensitivity analyses were conducted. Results Twenty-three cohort studies with a total of 58,219 patients were included, among which 31,750 (54.5%) patients had DM. The mean score of included studies evaluated by Newcastle-Ottawa Scale was 7.65, indicating moderate to high quality. The pooled results showed no significant difference in 1-year LTM (risk ratio [RR], 0.96; 95% CI 0.86-1.07) after amputation. However, 3-year (RR, 1.22; 95% CI 1.01-1.47) and 5-year (RR, 1.18; 95% CI 1.07-1.31) LTMs of DM patients were obviously higher than that of NDM (non-diabetes mellitus) patients. The STM of the DM group was significantly lower than the NDM group (RR, 0.80; 95% CI 0.64-0.98). Conclusions The current study revealed that DM patients had an obvious lower STM following LEA, but the risk of DM on LTM after amputation was gradually increased with time. More attention should be paid to the long-term survival of DM patients after LEA.

IntroductionThe revascularisation strategy for lower limb atherosclerosis obliterans (ASO) remains controversial. In this meta-analysis, we will summarise existing evidence to compare the long-term and short-term outcomes between endovascular revascularisation and open revascularisation for patients with ASO.MethodsRelevant randomised controlled trials (RCTs) and cohort studies are included from the following databases: MEDLINE/PubMed, Embase and the Cochrane Library. The last search time is 1 August 2022. Two reviewers will independently identify RCTs and cohort studies according to eligibility and exclusion criteria. The risk of bias of included cohort studies, and RCTs are assessed with the Newcastle-Ottawa Scale, Methodological Index of Non-randomized Studies and Cochrane Collaboration’s tool, respectively. The primary outcomes include overall survival, amputation-free survival and 30-day mortality. TSA Beta Software V.0.9.5.10 is used to perform the trial sequential analysis for primary outcomes. The Grades of Recommendations, Assessment, Development and Evaluation (GRADE) tool will be used to assess the level of evidence for outcome from RCTs. Stata V.17.0 software is used to pool primary outcomes.Ethics and disseminationThis study will be disseminated through peer-reviewed journals or conference reports. No ethical approval requirements are required because the results presented in this study are conducted based on published data.PROSPERO registration numberCRD42022359591

The tumor necrosis factor alpha (TNF-α) polymorphism may play an important role in chronic obstructive pulmonary disease (COPD) susceptibility. However, the results are still inconclusive. Eligible studies were searched in Cochrane Library database, EMBASE, Pudmed, Web of science, China National Knowledge Infrastructure, and Wanfang database. Finally, a total of 27 case-control studies with 3473 COPD cases and 4935 controls were included in the present analysis. We also performed trial sequential analysis (TSA) to confirm our results. Overall, association between TNF-α-308G/A polymorphism and COPD susceptibility was identified in allelic model (A vs. G, OR = 1.21, 95%CI: 1.01–1.45, p = 0.04) when smoking status was not adjusted. In ethnicity subgroup analysis, we found that the TNF-α -308G/A polymorphism was associated to COPD among Asians (GA vs. GG, OR = 1.35, 95%CI: 1.04–1.77, p = 0.02) when smoking status was not adjusted. However, no significant association was found in Asian smokers or Caucasian smokers. In conclusion, our study suggest that TNF-α-308 GA genotype is related to COPD in the Asian population. In addition, the TNF-α+489G/A, - 238G/A variants do not increase the risk of COPD.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021273980.